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Extramedullary myeloma
[[#pmid15257935|Rosinol et al. (2004)]] notes that extamedullary involvement by myeloma has been reported in 15-20% of patients at diagnosis, whilst in a further 15% during the course of the disease. [[#pmid8639427|Blade et al. (1996)]] report that 19% of patients with multiple myeloma younger than 40 years presented with extramedullary plasmacytomas. Similarly in an earlier study [[#pmid7964956|Blade et al. (1994)]] reported 19% of a study of patients with immunoglobulin D (IgD) multiple myeloma presented with extramedullary plasmacytomas. [[#pmid17594697|Huang et al. (2007)]] note a higher prevalence of extramedullary myeloma in patients younger than 55 years, in an epidemiology of multiple myeloma in Taiwan. [[#pmid15522061|Damaj et al. (2004)]] report a cumulative incidence of 4.6% of extramedullary myeloma. [[#pmid12031917|Alegre et al. (2002)]] found relapses with extramedullary manifestations in 14% of relapses after autologous peripheral blood stem cell transplantation. [[#pmid18462256|Cerny et al. (2008)]] report a 3.9% incidence rate of extramedullary myeloma. They also note that the median time of progression to extramedullary relapse was 29 months (range 9-64 months), and the median survival after diagnosis of the relapses was only 38 d (range 1-106 d). Mechanism On relapse extramedullary progression may be due to a change in the expression of certain adhesion molecules on the myeloma and or the bone marrow stromal cells. Clinical studies [[#pmid16930142|Mylin et al. (2006)]] found high levels of YKL-40 expression in extramedullary MM PCs from one extramedullary myeloma patient and in six HMCLs. [[#pmid19250676|Katodritou et al. (2009)]] ask whether there might be an association with precedent thalidomide administration and a correlation of special biological features. They found CD33 and CD117 positivity of bone marrow plasma cells in a high proportion of their extramedullary cases, and this was linked with poor outcome. [[#pmid18462256|Cerny et al. (2008)]] report that 5/6 of their extramedullary relapse cases showed immature/high-grade histology and CD56 was absent. In vitro studies [[#pmid19201468|Sheth et al. (2009)]] note that p53 nuclear expression, but not CD56 expression, is associated with disease progression to extramedullary sites in myeloma. ?Their study was based on paired bone marrow and extramedullary biopsies from 12 cases of myeloma. [[#pmid11841427|Dahl et al. (2002)]] report that CD44 expression was generally upregulated on extramedullary plasma cells whilst they showed an absence of CD56. Imaging [[#pmid16862493|Horger et al. (2006)]] provide imaging findings for cases of extramedullary myeloma (in German). Areas affected Cutaneous [[#pmid15953079|Alexandrescu et al. (2005)]] report a case of cutaneous plasmacytomas during the plasma cell leukaemia phase in a myeloma patient after treatment with thalidomide. [[#pmid11697498|Avigdor et al. (2001)]] report a case with extensive new plasmacytomas of the skin and nasal mucosa during thalidomide therapy. [[#pmid18450547|Molnar et al. (2008)]] and [[#pmid17851872|Varkonyi et al. (2008)]] report on plasmacytic skin infiltration in myeloma. [[#pmid18268398|Pirrotta et al. (2008)]] report on a case of extramedullary subcutaneous lesions during treatment with Bortezomib, albeit with a concomitant serum monoclonal protein reduction. [[#pmid19250676|Katodritou et al. (2009)]] include two cases of skin infiltration in their study. Central Nervous System [[#pmid15101714|Fassas et al. (2004)]] and [[#pmid11918539|Fassas et al. (2002)]] report on myeloma of the central nervous system. [[#pmid11697498|Avigdor et al. (2001)]] report a patient exhibiting neurological signs compatible with cranial nerve involvement and an MRI study was suggestive of a plasmacytoma involving the sellar region. [[#pmid18268398|Pirrotta et al. (2008)]] report on a case of extramedullary lesions in the central nervous system during treatment with Bortezomib, albeit with a concomitant serum monoclonal protein reduction. Pleural Myeloma spreading to the pleura is rare, affecting around 1% of cases. [[#pmid16085553|Kamble et al. (2005)]] describe the prognostic factors and poor outcome for cases of malignant pleural effusion with multiple myeloma. They note that Systemic chemotherapy comprising dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) and pleurodesis were effective in resolving the effusion but survival was short. High dose chemotherapy with peripheral blood stem cell support in six patients conferred no clear survival advantage. These patients died at median of four months from onset of the malignant effusion. [[#pmid18957845|Kim et al. (2008)]] provide a a case report and review of the literature (57 cases) for myelomatous pleural effusions. [[#pmid18019805|Attili et al. (2007)]] report a malignant myelomatous pleural effusion with good response to combination chemotherapy. [[#pmid17212026|Ghosh et al. (2006)]] report a myelomatous pleural effusion which initially responded to chemotherapy but subsequently recurred. Similarly [[#pmid10803706|Kim et al. (2000)]] report a case with a poor response to chemotherapy. Peritoneal [[#pmid18432366|Young et al. (2008)]] report a case of myelomatous ascites. Cardiac [[#pmid15621792|Abelman et al. (2005)]] report on cases of extramedullary myeloma representing as a pericardial effusion with tamponade. Hepatic [[#pmid15759959|del Giglio et al. (2005)]] report a case of hepatic plasmacytosis in a relapse after treatment with thalidomide. [[#pmid17348443|Galani et al. (2007)]] report a case with hepatic and renal plasma cell lesions in a myeloma patient whose bone marrow was still showing signs being in remission. Renal [[#pmid19250676|Katodritou et al. (2009)]] include two cases affecting the kidney. [[#pmid17348443|Galani et al. (2007)]] report a case with hepatic and renal plasma cell lesions in a myeloma patient whose bone marrow was still showing signs being in remission. Breast [[#pmid19250676|Katodritou et al. (2009)]] report on one case involving the breast. Lymph nodes [[#pmid19250676|Katodritou et al. (2009)]] study includes a case with lymph node involvement. Cranial [[#pmid19152712|Feller et al. (2009)]] report on a case of extramedullary myeloma in an HIV-seropositive subject. The extramedullary lesion affects the oral cavity, maxilla, parotid gland and paranasal sinuses, and extends intracranially and intraorbitally. Other [[#pmid16191086|Terpos et al. (2005)]] report on cases of extramedullary relapses post-high-dose therapy with plasmacytomas in the bone, skin, rectum, and testicles, in the absence of systemic progression. Treatment The results for treatment are mixed. [[#pmid16790518|Raanani et al. (2007)]] review the possible relationship between extramedullary disease and treatment with thalidomide and bortezomib for multiple myeloma. They note that a common explanation for extramedullary disease may simply be life prolongation by targeted treatments allowing for disease progression arising from cells hidden in sanctuary sites. Bortezomib [[#pmid16529604|Laura et al. (2006 )]] report on the effective use of bortezomib in cases of extramedullary myeloma. [[#pmid19250676|Katodritou et al. (2009)]] also found bortezomib to be effective for patients whose cells exhibited CD27. [[#pmid15710593|Patriarca et al. (2005)]] report on the successful treatment of a patient with bortezomib after extramedullary relapse (paraspinal and thoracic masses and multiple cranial nerve palsy). Hughes and Micallef-Eynaud (2006) report on a case with hepatic impairment caused by large intra-abdominal extramedullary plasmacytomas. Treatment with bortezomib and dexamethasone resulted in partial response of the plasmacytomas and complete resolution of his hepatic impairment. [[#pmid16001088|Paubelle et al. (2005)]] report a complete remission with bortezomib on plasmocytomas in an end-stage patient with refractory multiple myeloma who failed a range of other therapies including thalidomide. Use of intrapleural bortezomib in myelomatous pleural effusion. [[#pmid17979947|Iannitto et al. (2007)]] report on the intrapleural administration of bortezomib to tackle myelomatous pleural effusions. Although [[#pmid18268398|Pirrotta et al. (2008)]] report on a case where extramedullary subcutaneous lesions occurred during treatment with Bortezomib, albeit with a concomitant serum monoclonal protein reduction. IMiDs [[#pmid11803357|Biagi et al. (2001)]] report on the effectiveness of thalidomide in three cases of extramedullary relapse after allogeneic transplantation. [[#pmid16191086|Terpos et al. (2005)]] report on successful treatment with thalidomide for three cases of extramedullary relapse post autologous transplant. [[#pmid11380408|Blade et al. (2001)]] noted that none of the five patients with extramedullarly soft-tissue plasmacytomas responded to thalidomide, compared with 9/12 without an extramedullary relapse. [[#pmid15522061|Damaj et al. (2004)]] found the response to thalidomide was poor in patients with extramedullary myeloma. [[#pmid11722443|Myers et al. (2001)]] found a lack of response to thalidomide in extramedullary plasmacytomas, compared with a marked improvement in the abnormal protein levels. [[#pmid15257935|Rosinol et al. (2004)]] studied the response of patients with refractory/relapsed myeloma to thalidomide. The response rate was significantly higher in patients without extramedullary involvement. Although four of the 11 patients with extramedullary involvement had a serological response, a progression of the soft-tissue masses was observed in all of them. [[#pmid15061206|Anagnostopoulos et al. (2004)]] report on several cases of extramedullary relapse under thalidomide therapy, without increase of serum and/or urine monoclonal protein. Similarly [[#pmid18459108|Candoni et al. (2008)]] report extramedullary progression of multiple myeloma under thalidomide therapy despite concomitant response of medullary disease. Likewise [[#pmid11697498|Avigdor et al. (2001)]] report cases of extensive extramedullary progression during thalidomide therapy, despite a good response in the bone marrow. [[#pmid15218967|Okikawa et al. (2004)]] note that mature (MPC-1(+)/CD49e(+)) and intermediate (MPC-1(+)/CD49e(-)) myeloma cells were decreased by thalidomide therapy. However there was also a proliferation of immature myeloma cells showing MPC-1(-)/CD49e(-) phenotype and decreased intensity of CD38 expression, which may be a sign of progressive disease. They suggest that such immature myeloma cells may be resistant to thalidomide. [[#pmid16790518|Raanani et al. (2007)]] note that thalidomide needs the bone marrow microenvironment to exert its anti-myeloma effect and so is less effective on extramedullary myeloma cells. Radiotherapy [[#pmid16191086|Terpos et al. (2005)]] report on treatment with local radiotherapy for relapses with extramedullary plasmacytomas. References